Tsai Chang-Youh, Hsieh Song-Chou, Liu Chih-Wei, Lu Cheng-Hsun, Liao Hsien-Tzung, Chen Ming-Han, Li Ko-Jen, Wu Cheng-Han, Shen Cheih-Yu, Kuo Yu-Min, Yu Chia-Li
Division of Allergy, Immunology & Rheumatology, Taipei Veterans General Hospital, National Yang-Ming Chiao-Tung University, Taipei 11217, Taiwan.
Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei 10002, Taiwan.
Int J Mol Sci. 2021 May 26;22(11):5689. doi: 10.3390/ijms22115689.
Rheumatoid arthritis (RA) is a typical autoimmune-mediated rheumatic disease presenting as a chronic synovitis in the joint. The chronic synovial inflammation is characterized by hyper-vascularity and extravasation of various immune-related cells to form lymphoid aggregates where an intimate cross-talk among innate and adaptive immune cells takes place. These interactions facilitate production of abundant proinflammatory cytokines, chemokines and growth factors for the proliferation/maturation/differentiation of B lymphocytes to become plasma cells. Finally, the autoantibodies against denatured immunoglobulin G (rheumatoid factors), EB virus nuclear antigens (EBNAs) and citrullinated protein (ACPAs) are produced to trigger the development of RA. Furthermore, it is documented that gene mutations, abnormal epigenetic regulation of peptidylarginine deiminase genes 2 and 4 ( and ), and thereby the induced autoantibodies against PAD2 and PAD4 are implicated in ACPA production in RA patients. The aberrant expressions of non-coding RNAs (ncRNAs) including microRNAs (miRs) and long non-coding RNAs (lncRNAs) in the immune system undoubtedly derange the mRNA expressions of cytokines/chemokines/growth factors. In the present review, we will discuss in detail the expression of these ncRNAs and their target molecules participating in developing RA, and the potential biomarkers for the disease, its diagnosis, cardiovascular complications and therapeutic response. Finally, we propose some prospective investigations for unraveling the conundrums of rheumatoid pathogenesis.
类风湿关节炎（RA）是一种典型的自身免疫介导的风湿性疾病，表现为关节慢性滑膜炎。慢性滑膜炎症的特征是血管增生以及各种免疫相关细胞外渗，形成淋巴样聚集物，在其中固有免疫细胞和适应性免疫细胞之间发生密切的相互作用。这些相互作用促进了大量促炎细胞因子、趋化因子和生长因子的产生，以促进B淋巴细胞增殖/成熟/分化为浆细胞。最终，产生针对变性免疫球蛋白G（类风湿因子）、EB病毒核抗原（EBNA）和瓜氨酸化蛋白（ACPA）的自身抗体，从而引发RA的发展。此外，有文献记载，基因突变、肽基精氨酸脱亚氨酶基因2和4（以及）的异常表观遗传调控，以及由此诱导产生的针对PAD2和PAD4的自身抗体与RA患者ACPA的产生有关。包括微小RNA（miR）和长链非编码RNA（lncRNA）在内的非编码RNA（ncRNA）在免疫系统中的异常表达无疑会扰乱细胞因子/趋化因子/生长因子的mRNA表达。在本综述中，我们将详细讨论这些ncRNA及其参与RA发病的靶分子的表达，以及该疾病、其诊断、心血管并发症和治疗反应的潜在生物标志物。最后，我们提出了一些前瞻性研究，以解开类风湿发病机制的谜团。
